Effect of recombinant granulocyte colony-stimulating factor (rG-CSF) on chemotherapy-induced neutropenia in patients with urogenital cancer

Summary The effects of recombinant granulocyte colony-stimulating factor (rG-CSF) on the myelosuppression, especially neutropenia, induced by cancer chemotherapy in patients with urogenital cancer were investigated in a randomized, controlled clinical study. In this study, rG-CSF was given subcutaneously at a dose of 2 g/kg per day for 14 consecutive days. Changes in neutrophil counts were compared between the first (no rG-CSF) and second cycles (rG-CSF treatment period) of chemotherapy. rG-CSF administration was found to be effective in reducing the duration of neutropenia, in elevating the neutrophil nadir, and in reducing recovery time. Based on comparisons between the randomized rG-CSF treatment group (with rG-CSF) and the control group, treatment with rG-CSF resulted in the moderation or prevention of neutropenia and the acceleration of recovery. These results demonstrate that in chemotherapy of patients with urogenital cancer, in which neutropenia is a dose- or schedule-limiting factor, the concomitant use of rG-CSF may enable an increase in the dose (higher single dose or increased dose per unit of time) or shorten the chemotherapy period.     

Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.

PURPOSE: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC. EXPERIMENTAL DESIGN: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis. RESULTS: Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC. CONCLUSION: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.     

Transposable elements shape the human proteome landscape via formation of cis‐acting upstream open reading frames

Transposons are major drivers of mammalian genome evolution. To obtain new insights into the contribution of transposons to the regulation of protein translation, we here examined how transposons affected the genesis and function of upstream open reading frames (uORFs), which serve as cis‐acting elements to regulate translation from annotated ORFs (anORFs) located downstream of the uORFs in eukaryotic mRNAs. Among 39,786 human uORFs, 3,992 had ATG trinucleotides of a transposon origin, termed “transposon‐derived upstream ATGs” or TuATGs. Luciferase reporter assays suggested that many TuATGs modulate translation from anORFs. Comparisons with transposon consensus sequences revealed that most TuATGs were generated by nucleotide substitutions in non‐ATG trinucleotides of integrated transposons. Among these non‐ATG trinucleotides, GTG and ACG were converted into TuATGs more frequently, indicating a CpG methylation‐mediated process of TuATG formation. Interestingly, it is likely that this process accelerated human‐specific upstream ATG formation within transposon sequences in 5′ untranslated regions after divergence between human and nonhuman primates. Methylation‐mediated TuATG formation seems to be ongoing in the modern human population and could alter the expression of disease‐related proteins. This study shows that transposons have potentially been shaping the human proteome landscape via cis‐acting uORF creation.     

Clinical application of stress-breaking ball attachment for implant overdenture

PatientThe patient was a 62-year-old partially edentulous woman with missing bilateral premolars and molars in the mandibular jaw. The patient selected implant supported-removable partial denture rehabilitation. Implants were placed bilaterally at the distal extension of the denture base in order to minimize denture displacement. The stress-breaking ball (SBB) attachment consists of a flat-top ball head male and O-ring rubber female. The female was covered by a silicone housing with three amounts of space to allow three kinds of settlement (0.3 mm, 0.5 mm, and 0.7 mm); they were selected by thickness or pressure displacement of the mucosa and occlusal force. After the healing period, the SBB attachments (0.3 mm) were placed on the implants, and the implant-supported removable partial denture was then conventionally fabricated. The delivered denture had sufficient retention and appropriate stress breaking.DiscussionThe advantages of SBB attachments over conventional attachments are as follows: (1) they prevent the implant from excessive occlusal force, (2) they are ready-made, (3) they show appropriate retention, and (4) they can be easily mounted on the denture base. The disadvantages of these attachments are as follows: (1) they are approximately 1 mm higher than conventional ball attachments and (2) the retentive force cannot be adjusted.ConclusionThe use of a stress-breaking attachment for implant overdenture rehabilitation should be considered so that the occlusal force is equally distributed between the alveolar ridge and the implants.     

Head-out immersion in hot water increases serum BDNF in healthy males

Purpose: Brain-derived neurotrophic factor (BDNF) is an important neurotrophin. The present study investigated the effects of head-out water immersion (HOI) on serum BDNF concentrations.

Methods: Eight healthy men performed 20?min head-out water immersion at 42?°C (hot-HOI) and 35?°C (neutral-HOI). These experimental trials were administered in a randomised order separated by at least 7?days. Venous blood samples were withdrawn at rest, immediately after the 20-min HOI, as well as at 15 and 30?min after the end of the HOI. Serum BDNF and S100β, plasma cortisol, platelet and monocyte counts, and core body temperature (T_cb) were measured.

Results: T_cb was higher at the end of the hot-HOI and 15?min after hot-HOI (p?T_cb was recorded during neutral-HOI. BDNF level was higher (p?Conclusions: The present findings suggested that the increase in BDNF during 20-min hot-HOI was induced by hyperthermia through enhanced production, rather than by changes in permeability of the blood–brain barrier (BBB), platelet clotting mechanisms or secretion from monocytes.